Herpes simplex virus (HSV) keratitis is a major cause of corneal blindness in the Western World. The immunologic response of the host to the virus is believed to play a major role in determining whether an individual will develop a relatively benign, self-limited epithelial keratitis, or progress to a more severe form of the disease. Virus-determined factors influence the course of disease, as well. We have experimentally produced HSV keratitis in inbred mice, and find that the course of disease varies markedly, depending upon both the virus and host strain. We propose to exploit this model using genetically defined and immunologically well-characterized inbred mice to investigate immunologic, pathologic and genetic aspects of the virus-host interaction that determine the course of HSV keratitis. This model will be used to examine the histopathology of HSV stromal keratitis and to identify mechanisms by which certain inbred mouse strains are susceptible and others which are resistant to the disease. We will determine whether the establishment of latency is also under genetic control of the host as susceptibility/resistance to stromal keratitis appears to be. Congenic inbred mouse lines will be employed to identify gene(s) controlling resistance to HSV stromal keratitis. Immunoaffinity column-purified HSV glycoproteins and monoclonal antibodies, combined with standard immunologic assays will be used to search for an immunologic basis for susceptibility/resistance to HSV stromal keratitis. The influence of prior exposure to HSV on the subsequent course of HSV keratitis will be determined. Studies will be performed to determine whether occular disease produced by HSV in humans is similar to disease produced by the same virus isolate in mice. Information obtained from these studies may help to explain why some humans develop more visually debilitating forms of HSV ocular infection while others have relatively benign forms of disease. The data may suggest methods to modify the course of HSV in a sight-saving way in humans.